{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:55:21Z","timestamp":1783698921959,"version":"3.55.0"},"reference-count":26,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T00:00:00Z","timestamp":1673481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The National Science Centre (NCN), Poland","award":["2019\/35\/O\/ST5\/02746"],"award-info":[{"award-number":["2019\/35\/O\/ST5\/02746"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>MicroRNAs (miRNAs) have great therapeutic potential; however, their delivery still faces huge challenges, especially given the short half-life of naked miRNAs due to rapid hydrolysis or inactivation by abundant nucleases in the systemic circulation. Therefore, the search for reliable miRNA delivery systems is crucial. Nanogels are one of the more effective nanocarriers because they are biocompatible and have a high drug-loading capacity. In this study, acrylamide-based nanogels containing cationic groups and redox-sensitive crosslinkers were developed for cellular delivery of anti-miR21 (a-miR21). To achieve this, post-polymerization loading of a-miR21 oligonucleotides into nanogels was performed by utilizing the electrostatic interaction between positively charged nanogels and negatively charged oligonucleotides. Different molar ratios of the amine groups (N) on the cationic nanogel and phosphate groups (P) on the miRNA were investigated. An N\/P ratio of 2 allowed high miRNA loading capacity (MLC, 6.7% w\/w) and miRNA loading efficiency (MLE, 99.7% w\/w). Successful miRNA loading was confirmed by dynamic light scattering (DLS) and electrophoretic light scattering (ELS) measurements. miRNA-loaded nanogels (NG\/miRNA) formed stable dispersions in biological media and showed an enhanced miRNA release profile in the presence of glutathione (GSH). Moreover, the addition of heparin to dissociate the miRNA from the cationic nanogels resulted in the complete release of miRNA. Lastly, a cell uptake study indicated that NG\/miRNA could be easily taken up by cancer cells.<\/jats:p>","DOI":"10.3390\/molecules28020761","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T04:29:38Z","timestamp":1673497778000},"page":"761","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Simple Synthesis of Reduction-Responsive Acrylamide-Type Nanogels for miRNA Delivery"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3807-4446","authenticated-orcid":false,"given":"Ali","family":"Maruf","sequence":"first","affiliation":[{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland"},{"name":"Biotechnology Center, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Milewska","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland"},{"name":"Biotechnology Center, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4856-9821","authenticated-orcid":false,"given":"Anna","family":"Lalik","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland"},{"name":"Department of Systems Biology and Engineering, Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1812-5496","authenticated-orcid":false,"given":"Sebastian","family":"Student","sequence":"additional","affiliation":[{"name":"Biotechnology Center, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland"},{"name":"Department of Systems Biology and Engineering, Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6592-4875","authenticated-orcid":false,"given":"Ilona","family":"Wandzik","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 4, 44-100 Gliwice, Poland"},{"name":"Biotechnology Center, Silesian University of Technology, Krzywoustego 8, 44-100 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":"MicroRNAs: Small RNAs with a big role in gene regulation","volume":"5","author":"He","year":"2004","journal-title":"Nat. Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15004","DOI":"10.1038\/sigtrans.2015.4","article-title":"The role of MicroRNAs in human cancer","volume":"1","author":"Peng","year":"2016","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/sj.bjc.6603023","article-title":"MicroRNAs in cell proliferation, cell death, and tumorigenesis","volume":"94","author":"Hwang","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s10555-017-9712-y","article-title":"MicroRNAs and metastasis: Small RNAs play big roles","volume":"37","author":"Kim","year":"2018","journal-title":"Cancer Metastasis Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1080\/15476286.2019.1582956","article-title":"Extracellular microRNAs exhibit sequence-dependent stability and cellular release kinetics","volume":"16","author":"Pauwels","year":"2019","journal-title":"RNA Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e252","DOI":"10.1038\/mtna.2015.23","article-title":"siRNA Versus miRNA as Therapeutics for Gene Silencing","volume":"4","author":"Lam","year":"2015","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s41544-019-0024-y","article-title":"Recent progress in microRNA-based delivery systems for the treatment of human disease","volume":"1","author":"Fu","year":"2019","journal-title":"ExRNA"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dasgupta, I., and Chatterjee, A. (2021). Recent Advances in miRNA Delivery Systems. Methods Protoc., 4.","DOI":"10.3390\/mps4010010"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/2277-9175.98152","article-title":"Viral and nonviral delivery systems for gene delivery","volume":"1","author":"Nayerossadat","year":"2012","journal-title":"Adv. Biomed. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8564","DOI":"10.1021\/cr500131f","article-title":"Biodegradable Polymer Nanogels for Drug\/Nucleic Acid Delivery","volume":"115","author":"Li","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"401","DOI":"10.4155\/tde-2020-0030","article-title":"Is nanoparticle functionalization a versatile approach to meet the challenges of drug and gene delivery?","volume":"11","author":"Pinelli","year":"2020","journal-title":"Ther. Deliv."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jconrel.2016.08.029","article-title":"Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy","volume":"239","author":"Shatsberg","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ajps.2018.10.006","article-title":"Redox-sensitive, PEG-shielded carboxymethyl PEI nanogels silencing MicroRNA-21, sensitizes resistant ovarian cancer cells to cisplatin","volume":"15","author":"Javanmardi","year":"2020","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1021\/acs.biomac.8b01553","article-title":"Nanogels Enable Efficient miRNA Delivery and Target Gene Downregulation in Transfection-Resistant Multiple Myeloma Cells","volume":"20","author":"Zilkowski","year":"2019","journal-title":"Biomacromolecules"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"449","DOI":"10.34172\/bi.2022.23263","article-title":"PEGylated nanohydrogels delivering anti-MicroRNA-21 suppress ovarian tumor-associated angiogenesis in matrigel and chicken chorioallantoic membrane models","volume":"12","author":"Javanmardi","year":"2022","journal-title":"Bioimpacts"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/adma.201403387","article-title":"Efficient delivery of therapeutic miRNA nanocapsules for tumor suppression","volume":"27","author":"Liu","year":"2015","journal-title":"Adv. Mater."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"52039","DOI":"10.1039\/C7RA09797B","article-title":"Nanogel-antimiR-31 conjugates affect colon cancer cells behaviour","volume":"7","author":"Dispenza","year":"2017","journal-title":"RSC Adv."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.jconrel.2010.05.031","article-title":"Efficient siRNA delivery based on PEGylated and partially quaternized polyamine nanogels: Enhanced gene silencing activity by the cooperative effect of tertiary and quaternary amino groups in the core","volume":"146","author":"Tamura","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12198","DOI":"10.1002\/chem.202101924","article-title":"Self-Assembled Cationic Polypeptide Supramolecular Nanogels for Intracellular DNA Delivery","volume":"27","author":"Rentmeister","year":"2021","journal-title":"Chemistry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3160","DOI":"10.1021\/mp300255p","article-title":"Intracellular delivery of DNA and enzyme in active form using degradable carbohydrate-based nanogels","volume":"9","author":"Ahmed","year":"2012","journal-title":"Mol. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"671","DOI":"10.3109\/1354750X.2012.715672","article-title":"Glutathione levels in human tumors","volume":"17","author":"Gamcsik","year":"2012","journal-title":"Biomarkers"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.jconrel.2011.01.030","article-title":"Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery","volume":"152","author":"Cheng","year":"2011","journal-title":"J. Control. Release"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.omtn.2020.03.003","article-title":"The Promising Role of miR-21 as a Cancer Biomarker and Its Importance in RNA-Based Therapeutics","volume":"20","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"212969","DOI":"10.1016\/j.bioadv.2022.212969","article-title":"Trehalose-releasing nanogels: A step toward a trehalose delivery vehicle for autophagy stimulation","volume":"138","author":"Maruf","year":"2022","journal-title":"Biomater. Adv."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Maruf, A., Milewska, M., Lalik, A., and Wandzik, I. (2022). pH and Reduction Dual-Responsive Nanogels as Smart Nanocarriers to Resist Doxorubicin Aggregation. Molecules, 27.","DOI":"10.3390\/molecules27185983"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Wu, J. (2021). The Enhanced Permeability and Retention (EPR) Effect: The Significance of the Concept and Methods to Enhance Its Application. J. Pers. Med., 11.","DOI":"10.3390\/jpm11080771"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/2\/761\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:04:01Z","timestamp":1760119441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/28\/2\/761"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,12]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["molecules28020761"],"URL":"https:\/\/doi.org\/10.3390\/molecules28020761","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,12]]}}}